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乙型肝炎病毒X蛋白诱导的异常微小RNA表达对肝细胞癌发病机制的作用

Contribution of hepatitis B virus X protein-induced aberrant microRNA expression to hepatocellular carcinoma pathogenesis.

作者信息

Wei Zhiyuan, Shen Xiaohe, Ni Bing, Luo Gaoxing, Tian Yi, Sun Yi

机构信息

Institute of Immunology, PLA, Army Medical University (Third Military Medical University) , Chongqing , P.R. China.

Southwest Hospital, Army Medical University (Third Military Medical University) , Chongqing , P. R. China.

出版信息

Turk J Biol. 2019 Apr 5;43(2):113-123. doi: 10.3906/biy-1807-196. eCollection 2019.

DOI:10.3906/biy-1807-196
PMID:31320813
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6620039/
Abstract

The hepatitis B virus-encoded X (HBX) protein plays important roles in Hepatocellular carcinoma (HCC). Previous studies have demonstrated that HBX can induce alterations in the expression of numerous microRNAs (miRNAs) involved in the carcinogenesis of various tumors. However, the global profile of liver miRNA changes induced by HBX has not been characterized. In this study, we conducted a miRNA microarray analysis to investigate the influence of HBX on the expression of total miRNAs in liver in relation to HCC. Comparative analysis of the data from human normal liver cells (L02) and human HCC cells (HepG2), with or without HBX, identified 19 differentially expressed miRNAs, including 5 with known association to HBX. Target gene prediction for the aberrantly expressed miRNAs identified a total of 304 potential target genes, involved in sundry pathways. Finally, pathway analysis of the HBXinduced miRNAs pathway showed that 5 of the total miRNAs formed an internetwork, suggesting that HBX might exert its pathological effects on hepatic cells through functional synergy with miRNAs that regulated common pathways in liver cells. Therefore, this work provides new insights into the mechanisms of HCC as well as potential diagnostic markers or therapeutic targets for use in clinical management of HCC.

摘要

乙型肝炎病毒编码的X蛋白（HBX）在肝细胞癌（HCC）中发挥着重要作用。先前的研究表明，HBX可诱导多种参与各种肿瘤发生的微小RNA（miRNA）表达发生改变。然而，HBX诱导的肝脏miRNA变化的整体情况尚未得到描述。在本研究中，我们进行了miRNA微阵列分析，以研究HBX对与HCC相关的肝脏中总miRNA表达的影响。对来自人正常肝细胞（L02）和人HCC细胞（HepG2）、有无HBX的数据进行比较分析，鉴定出19种差异表达的miRNA，其中5种与HBX有已知关联。对异常表达的miRNA进行靶基因预测，共鉴定出304个潜在靶基因，涉及多种途径。最后，对HBX诱导的miRNA途径进行通路分析表明，总miRNA中的5种形成了一个网络，提示HBX可能通过与调节肝细胞共同通路的miRNA功能协同作用对肝细胞发挥其病理作用。因此，这项工作为HCC的发病机制以及HCC临床管理中潜在的诊断标志物或治疗靶点提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/0c6e06b4448d/turkjbio-43-113-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/35fb959303da/turkjbio-43-113-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/8f6d679b555a/turkjbio-43-113-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/6d9942f03f28/turkjbio-43-113-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/5cde82aafd6a/turkjbio-43-113-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/60dc4456fa92/turkjbio-43-113-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/0c6e06b4448d/turkjbio-43-113-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/35fb959303da/turkjbio-43-113-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/8f6d679b555a/turkjbio-43-113-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/6d9942f03f28/turkjbio-43-113-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/5cde82aafd6a/turkjbio-43-113-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/60dc4456fa92/turkjbio-43-113-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/6620039/0c6e06b4448d/turkjbio-43-113-g006.jpg

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